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Abstract

Background: Apoptosis plays an important role in progression of heart failure. While membrane bound apoptotic molecules like TRAIL or FAS have shown to be pro-apoptotic, the effect of their soluble form is unclear. We assessed the hypothesis that soluble molecules of apoptosis are associated with the prognosis of heart failure patients.

Methods: To study the role of soluble TRAIL (sTRAIL), soluble FAS (sFAS), and TNF-alpha in heart failure we enrolled 360 patients with advanced heart failure (mean age 72 ± 13 years, 35% of female gender, BNP 678.98 ± 760.45 pg/ml). 174 patients (48%) experienced an event (death and/or rehospitalization) during the median follow-up time of 16 months (15–17 months). Plasma levels of the different proteins were determined using specific ELISAs at baseline.

Results: Using Cox regression we found a significant protective influence of sTRAIL on survival with a crude proportional hazard ratio (HR) of 0.58 (95% Confidence Interval (CI): 0.4–0.84) comparing third to first tertile (P=0.004). In contrast, sFAS was associated with a poor prognosis with a crude HR of 2.26 (95% CI: 1.54–3.3, P<0.001) in the third tertile compared to the first tertile. There was a non-significant trend for TNF-alpha (crude HR: 1.34, 95% CI: .93–1.94, P=0.12). Only sFAS remained an independent risk predictor of outcome after adjustment for age, gender, BNP, impaired kidney function, coronary artery disease, history of hypertension and diabetes with a HR of 1.52 (95% CI: 1–2.29, P=0.048) comparing third to first tertile.

Conclusion: sFAS is an independent risk predictor besides BNP of death and rehospitalization in patients with advanced heart failure.